Harmonizing Enzyme-like Cofactors to Boost Nanozyme Catalysis.

Engineering isolated metal sites resembling the primary coordination sphere of metallocofactors enables atomically dispersed materials as promising nanozymes. However, most existing nanozymes primarily focus on replicating specific metallocofactors while neglecting other supporting cofactors within active pockets, leading to reduced electron transfer (ET) efficiency and thus inferior catalytic performances. Herein, we report a metal-organic framework UiO-67 nanozyme with atomically dispersed iron sites, which involves multiple tailored enzyme-like nanocofactors that synergistically drive the ET process for enhanced peroxidase-like catalysis. Among them, the linker-coupled atomic iron site plays a critical role in substrate activation, while bare linkers and zirconia nodes facilitate the ET efficiency of intermediates. The synergy of three nanocofactors results in a 4.29-fold enhancement compared with the single effort of isolated metal site-based nanocofactor, holding promise in immunoassay for sensitive detection of chlorpyrifos. This finding opens a new way for designing high-performance nanozymes by harmonizing various nanocofactors at the atomic and molecular scale.

Effect of Phosphorus Modulation in Iron Single-Atom Catalysts for Peroxidase Mimicking.

Fe-N-C single-atom catalysts (SACs) exhibit excellent peroxidase (POD)-like catalytic activity, owing to their well-defined isolated iron active sites on the carbon substrate, which effectively mimic the structure of natural peroxidase's active center. To further meet the requirements of diverse biosensing applications, SAC POD-like activity still needs to be continuously enhanced. Herein, a phosphorus (P) heteroatom is introduced to boost the POD-like activity of Fe-N-C SACs. A 1D carbon nanowire (FeNCP/NW) catalyst with enriched Fe-N4 active sites is designed and synthesized, and P atoms are doped in the carbon matrix to affect the Fe center through long-range interaction. The experimental results show that the P-doping process can boost the POD-like activity more than the non-P-doped one, with excellent selectivity and stability. The mechanism analysis results show that the introduction of P into SAC can greatly enhance POD-like activity initially, but its effect becomes insignificant with increasing amount of P. As a proof of concept, FeNCP/NW is employed in an enzyme cascade platform for highly sensitive colorimetric detection of the neurotransmitter acetylcholine.

Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review.

Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approval by the FDA, tianeptine has been distributed online and at small retail locations. The term "gas station drugs" refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as "Zaza" and "Tianna Red." It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances.

Photoexcited Ru single-atomic sites for efficient biomimetic redox catalysis.

The unsatisfactory catalytic activity of nanozymes owing to their inefficient electron transfer (ET) is the major challenge in biomimetic catalysis-related biomedical applications. Inspired by the photoelectron transfers in natural photoenzymes, we herein report a photonanozyme of single-atom Ru anchored on metal-organic frameworks (UiO-67-Ru) for achieving photoenhanced peroxidase (POD)-like activity. We demonstrate that the atomically dispersed Ru sites can realize high photoelectric conversion efficiency, superior POD-like activity (7.0-fold photoactivity enhancement relative to that of UiO-67), and good catalytic specificity. Both in situ experiments and theoretical calculations reveal that photoelectrons follow the cofactor-mediated ET process of enzymes to promote the production of active intermediates and the release of products, demonstrating more favorable thermodynamics and kinetics in H2O2 reduction. Taking advantage of the unique interaction of the Zr-O-P bond, we establish a UiO-67-Ru-based immunoassay platform for the photoenhanced detection of organophosphorus pesticides.

The Management of Recurrent Post-myelography Lumbar Pseudomeningocele With Epidural Blood Patch.

Pseudomeningoceles are a well-known potential postoperative complication of spinal and cranial surgeries that can occur after lumbar decompression and posterior fossa surgeries. They are often caused by incidental durotomies but may also occur as a result of dural puncture during diagnostic testing. This report describes a 59-year-old male that developed a recurrent pseudomeningocele after an L4 laminectomy for severe lumbar spinal stenosis that was ultimately treated with an epidural blood patch (EBP). His preoperative condition greatly improved, but he developed a pseudomeningocele that did not resolve after applying ice and light pressure. The patient subsequently underwent a wound exploration where no dural defect was identified. During this exploration, the dura was reinforced with dural onlays and sealant. Unfortunately, the patient developed another pseudomeningocele within a short interval. It was then suspected that the post-laminectomy site provided a space for the dural punctures from previous CT myelography to leak cerebrospinal fluid (CSF) into. The patient subsequently underwent ultrasound (US)-guided aspiration of the pseudomeningocele and EBP injections at the levels where his preoperative myelography was performed. The success of the EBP indicates that the previous CT myelography was the likely cause of the pseudomeningocele. Recurrent spinal pseudomeningoceles with no evidence of incidental durotomy may be caused by dural puncture from myelography. In such cases, EBP to the area that the previous myelography was performed can resolve the pseudomeningocele.

Single-Atom Ce-N4-C-(OH)2 Nanozyme-Catalyzed Cascade Reaction to Alleviate Hyperglycemia.

The enzyme-mimicking catalytic activity of single-atom nanozymes has been widely used in tumor treatment. However, research on alleviating metabolic diseases, such as hyperglycemia, has not been reported. Herein, we found that the single-atom Ce-N4-C-(OH)2 (SACe-N4-C-(OH)2) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N4-C-(OH)2 nanozyme initiated a cascade reaction involving superoxide dismutase-, oxidase-, catalase-, and peroxidase-like activity to overcome the limitations associated with the substrate and produce •OH, thus improving glucose intolerance and insulin resistance by increasing the phosphorylation of protein kinase B and glycogen synthase kinase 3ß, and the expression of glycogen synthase, promoting glycogen synthesis to improve glucose intolerance and insulin resistance in high-fat diet-induced hyperglycemic mice. Altogether, these results demonstrated that the novel nanozyme SACe-N4-C-(OH)2 alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.

Engineering Atomic Single Metal-FeN4Cl Sites with Enhanced Oxygen-Reduction Activity for High-Performance Proton Exchange Membrane Fuel Cells.

Fe-N-C single-atomic metal site catalysts (SACs) have garnered tremendous interest in the oxygen reduction reaction (ORR) to substitute Pt-based catalysts in proton exchange membrane fuel cells. Nowadays, efforts have been devoted to modulating the electronic structure of metal single-atomic sites for enhancing the catalytic activities of Fe-N-C SACs, like doping heteroatoms to modulate the electronic structure of the Fe-Nx active center. However, most strategies use uncontrolled long-range interactions with heteroatoms on the Fe-Nx substrate, and thus the effect may not precisely control near-range coordinated interactions. Herein, the chlorine (Cl) is used to adjust the Fe-Nx active center via a near-range coordinated interaction. The synthesized FeN4Cl SAC likely contains the FeN4Cl active sites in the carbon matrix. The additional Fe-Cl coordination improves the instrinsic ORR activity compared with normal FeNx SAC, evidenced by density functional theory calculations, the measured ORR half-wave potential (E1/2, 0.818 V), and excellent membrane electrode assembly performance.

Atomically dispersed Ru3 site catalysts for electrochemical sensing of small molecules.

Rational design and construction of electrochemical sensing platforms with high sensitivity and selectivity is one of the challenges in practical application. Although single-atom catalysts (SACs) have attracted extensive attention, atomically dispersed metal catalysts (ADCs) with multi-atom sites can further compensate for the deficiencies of SACs, which have gradually been a research hotspot in recent years. Herein, atomically dispersed Ru3 site catalyst (Ru3/NC) is employed to catalyze small biomolecule oxidation, which exhibits much superior electrocatalytic ability of uric acid (UA) to Ru single-atom catalyst (Ru1/NC). What's more, theoretical calculations reveal that the enhanced performance is mainly derived from the dominant electronic structure of ADCs with multi-atom sites compared to SACs, leading to the more favorable adsorption of hydroxy anion groups, which can serve as one part of the active moiety and "promoter" to achieve the fast oxidation of small biomolecules. Our findings provide a new paradigm for designing promising catalysts to realize highly sensitive and selective small biomolecule detection and explore the catalytic mechanisms of small biomolecules at the atomic scale.

Modulating Nucleus Oxygen Concentration by Altering Intramembrane Cholesterol Levels: Creating Hypoxic Nucleus in Oxic Conditions.

We propose a novel mechanism by which cancer cells can modulate the oxygen concentration within the nucleus, potentially creating low nuclear oxygen conditions without the need of an hypoxic micro-environment and suited for allowing cancer cells to resist chemo- and radio-therapy. The cells ability to alter intra-cellular oxygen conditions depends on the amount of cholesterol present within the cellular membranes, where high levels of cholesterol can yield rigid membranes that slow oxygen diffusion. The proposed mechanism centers on the competition between (1) the diffusion of oxygen within the cell and across cellular membranes that replenishes any consumed oxygen and (2) the consumption of oxygen in the mitochondria, peroxisomes, endoplasmic reticulum (ER), etc. The novelty of our work centers around the assumption that the cholesterol content of a membrane can affect the oxygen diffusion across the membrane, reducing the cell ability to replenish the oxygen consumed within the cell. For these conditions, the effective diffusion rate of oxygen becomes of the same order as the oxygen consumption rate, allowing the cell to reduce the oxygen concentration of the nucleus, with implications to the Warburg Effect. The cellular and nucleus oxygen content is indirectly evaluated experimentally for bladder (T24) cancer cells and during the cell cycle, where the cells are initially synchronized using hydroxeaurea (HU) at the late G1-phase/early S-phase. The analysis of cellular and nucleus oxygen concentration during cell cycle is performed via (i) RT-qPCR gene analysis of hypoxia inducible transcription factors (HIF) and prolyl hydroxylases (PHD) and (ii) radiation clonogenic assay every 2 h, after release from synchronization. The HIF/PHD genes allowed us to correlate cellular oxygen with oxygen concentration in the nucleus that is obtained from the cells radiation response, where the amount DNA damage due to radiation is directly related to the amount of oxygen present in the nucleus. We demonstrate that during the S-phase cells can become hypoxic in the late S-phase/early G2-phase and therefore the radiation resistance increases 2- to 3-fold.

An Ion-Imprinting Derived Strategy to Synthesize Single-Atom Iron Electrocatalysts for Oxygen Reduction.

Carbon-based single-atom catalysts (CSACs) have recently received extensive attention in catalysis research. However, the preparation process of CSACs involves a high-temperature treatment, during which metal atoms are mobile and aggregated into nanoparticles, detrimental to the catalytic performance. Herein, an ion-imprinting derived strategy is proposed to synthesize CSACs, in which isolated metal-nitrogen-carbon (Me-N4 -Cx ) moiety covalently binds oxygen atoms in Si-based molecular sieve frameworks. Such a feature makes Me-N4 -Cx moiety well protected/confined during the heat treatment, resulting in the final material enriched with single-atom metal active sites. As a proof of concept, a single-atom Fe-N-C catalyst is synthesized by using this ion-imprinting derived strategy. Experimental results and theoretical calculations demonstrate high concentration of single FeN4 active sites distributed in this catalyst, resulting in an outstanding oxygen reduction reaction (ORR) performance with a half-wave potential of 0.908 V in alkaline media.

Single-Atom Ir-Anchored 3D Amorphous NiFe Nanowire@Nanosheets for Boosted Oxygen Evolution Reaction.

The establishment of advanced electrocatalysts with remarkable performance and cost effectiveness for the oxygen evolution reaction (OER) is an emerging need for the production of clean hydrogen fuel. In this work, three-dimensional (3D) amorphous NiFeIrx/Ni core-shell nanowire@nanosheets (NW@NSs) are successfully synthesized through a facile one-step reduction process with atomically isolated Ir atoms anchored on an NiFe-based core. By taking advantage of their unique structure and composition, the resultant NiFeIrx/Ni NW@NSs have a high electrocatalytic activity for OER which can deliver current densities of 10 and 100 mA cm-2 at overpotentials as low as 200 and 250 mV in 1 M KOH, respectively. It is worth noting that NiFeIrx/Ni NW@NSs exhibit outstanding long-term stability over 12 h at a current density of 10 mA cm-2. Theoretical calculations also reveal that the intrinsic activity of the resultant NiFeIrx/Ni NW@NSs is significantly enhanced upon the addition of Ir single atoms, highlighting the critical role of the synergistic effect between Ir single atoms and the support. Due to their easy synthesis and superior electrochemical performance, the newly designed nanostructures may find promising potential applications in water splitting and other related fields.

A data-informatics method to quantitatively represent ternary eutectic microstructures.

Many of the useful properties of modern engineering materials are determined by the material's microstructure. Controlling the microstructure requires an understanding of the complex dynamics underlying its evolution during processing. Investigating the thermal and mass transport phenomena responsible for a structure requires establishing a common language to quantitatively represent the microstructures being examined. Although such a common language exists for some of the simple structures, which has allowed these materials to be engineered, there has yet to be a method to represent complex systems, such as the ternary microstructures, which are important for many technologies. Here we show how stereological and data science methods can be combined to quantitatively represent ternary eutectic microstructures relative to a set of exemplars that span the stereological attribute space. Our method uniquely describes ternary eutectic microstructures, allowing images from different studies, with different compositions and processing histories, to be quantitatively compared. By overcoming this long-standing challenge, it becomes possible to begin to make progress toward a quantitatively predictive theory of ternary eutectic growth. We anticipate that the method of quantifying instances of an object relative to a set of exemplars spanning attribute-space will be broadly applied to classify materials structures, and may also find uses in other fields.

Sugar Blowing-Induced Porous Cobalt Phosphide/Nitrogen-Doped Carbon Nanostructures with Enhanced Electrochemical Oxidation Performance toward Water and Other Small Molecules.

Rational design of high active and robust nonprecious metal catalysts with excellent catalytic efficiency in oxygen evolution reaction (OER) is extremely vital for making the water splitting process more energy efficient and economical. Among these noble metal-free catalysts, transition-metal-based nanomaterials are considered as one of the most promising OER catalysts due to their relatively low-cost intrinsic activities, high abundance, and diversity in terms of structure and morphology. Herein, a facile sugar-blowing technique and low-temperature phosphorization are reported to generate 3D self-supported metal involved carbon nanostructures, which are termed as Co2 P@Co/nitrogen-doped carbon (Co2 P@Co/N-C). By capitalizing on the 3D porous nanostructures with high surface area, homogeneously dispersed active sites, the intimate interaction between active sites, and 3D N-doped carbon, the resultant Co2 P@Co/N-C exhibits satisfying OER performance superior to CoO@Co/N-C, delivering 10 mA cm-2 at overpotential of 0.32 V. It is worth noting that in contrast to the substantial current density loss of RuO2 , Co2 P@Co/N-C shows much enhanced catalytic activity during the stability test and a 1.8-fold increase in current density is observed after stability test. Furthermore, the obtained Co2 P@Co/N-C can also be served as an excellent nonprecious metal catalyst for methanol and glucose electrooxidation in alkaline media, further extending their potential applications.

Creation and destruction of morphotropic phase boundaries through electrical poling: a case study of lead-free (Bi(1/2)Na(1/2))TiO3-BaTiO3 piezoelectrics.

We report the first direct evidence that the morphotropic phase boundary in ferroelectric materials, along with the associated strong piezoelectricity, can be created, destroyed, or even replaced by another morphotropic phase boundary through phase transitions during electrical poling. The real-time evolution of crystal structure and domain morphology during the poling-induced phase transitions in (Bi(1/2)Na(1/2))TiO3}BaTiO3 is observed with in situ transmission electron microscopy. These observations elucidate the microstructural origin of the macroscopic piezoelectricity's dependence on the poling field and previously unexplained strain behaviors. This study demonstrates that the ferroelectric-to-ferroelectric transitions during the poling process can completely alter the morphotropic phase boundaries and, hence, must be comprehensively investigated when interpreting the microscopic mechanism of macroscopic piezoelectric behaviors.